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Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications

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Abstract

Background

Familial breast cancer accounts for 20–30 % of all breast cancer cases. Mutations in the BRCA1 and BRCA2 genes account for the majority of high risk families with both early onset breast cancer and ovarian cancer. Most of the families with less than six breast cancer cases and no ovarian cancer do not carry BRCA1 or BRCA2 mutations that can be detected using routine sequencing protocols. Here, we aimed to review the etiology of familial breast cancer in cases without BRCA1 and BRCA2 mutations.

Results

After excluding BRCA1 and BRCA2 mutations, factors proposed to contribute to familial breast cancer include: chance clustering of apparently sporadic cases, shared lifestyle, monogenic inheritance, i.e., dominant gene mutations associated with a high risk (TP53, PTEN, STK11), dominant gene mutations associated with a relatively low risk (ATM, BRIP1, RLB2), recessive gene mutations associated with horizontal inheritance patterns (sister-sister), and polygenic inheritance where susceptibility to familial breast cancer is thought to be conferred by a large number of low risk alleles.

Conclusions

Current evidence suggests that in the majority of cases with BRCA1 and BRCA2 negative familial breast cancer the etiology is due to interactions of intermediate or low risk alleles with environmental and lifestyle factors. Thus, a careful selection of patients submitted to genetic testing is needed. Clearly, further research is required to fully elucidate the etiology of non-BRCA familial breast cancer.

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  1. Department of Basic Medical Lessons Faculty of Health and Caring Professions, Technological Educational Institute of Athens, Eleutheriou Benizelou 106 Kallithea, 17676, Athens, Greece

    Eugenia Yiannakopoulou

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Yiannakopoulou, E. Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications. Cell Oncol. 37, 1–8 (2014). https://doi.org/10.1007/s13402-013-0158-0

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